ADAMs

Supporting information

ADAMs (a disintegrin and metalloproteases) are a family of transmembrane metalloproteinases that function as proteases and/or adhesion molecules. They are members of the M12B adamalysin protease subfamily, which also includes reprolysins and ADAMTs. There have been 25 human ADAM genes identified to date, 21 of them are functional, and 13 have proteolytic activity. The ADAMs with proteolytic activity are ADAMDEC-1, ADAM-8, 9, 10, 12, 15, 17, 19, 20, 21, 28, 30 and 33, while ADAM-2, 7, 11, 18, 22, 23, 29 and 32 are catalytically inactive, and have roles in protein folding and protein-protein interaction.

The ADAM family has a varied tissue distribution profile. ADAM-2, 18, 20, 21, 29 and 30 are primarily expressed in the testes and have been associated with fertility, consistent with their role in spermatogenesis and sperm-egg interaction. The other ADAMs are expressed in a variety of tissues and have been associated with biological processes such as cell fate determination in the nervous system, axon guidance, cell migration, muscle development, immunity and wound healing.

Proteolytic ADAMs function by cleaving transmembrane proteins, such as cytokines, chemokines and growth factors, to modulate their activity. Cleavage of the protein's ectodomain, a process termed 'shedding', results in the transmembrane and cytoplasmic domains being released into the cytoplasm. This mechanism regulates substrate activity by either resulting in a non-functional cell surface molecule, or inducing signal transduction through the release of intracellular or extracellular components. Non-proteolytic ADAMs interact with integrins to either positively or negatively regulate cell-cell adhesion. ADAM activity is regulated endogenously by TIMPs (tissue inhibitors of metalloproteinases), although ADAM-8, 9 and 19 are insensitive to TIMP inhibition.

ADAM substrates include EGF, TNF-α, Notch and amyloid precursor protein (APP). EGF and TNF-α require cleavage by ADAM-17 before being released from the cell membrane and binding to their receptors to initiate signaling. Following ligand binding Notch is cleaved by ADAM-10 and then γ-secretase, releasing the intracellular component of Notch, and initiating Notch signaling. ADAM-10 and 17 have been shown to act as α-secretases, and are therefore able to cleave APP to form soluble APPsα. Overexpression of ADAM-10 has been shown to reduce amyloid plaque formation and improve cognitive deficits in a mouse model of Alzheimer's disease (AD).

ADAMs have been implicated in cancer, being involved in the promotion of tumor invasion and metastasis, as well as having a role in breast cancer through the initiation of EGF receptor signaling. ADAMs may also be important in the pathology of neurological and cardiovascular diseases, including AD and atherosclerosis, as well as in asthma, inflammation, rheumatoid arthritis and diabetes.

To view external sources of pharmacological information for ADAMs, please click here: IUPHAR Receptor Code

View all products for ADAMs »
Gene Species Gene Symbol Gene Accession No. Protein Accession No.
ADAM10 Human ADAM10 NM_001110 O14672
Mouse Adam10 NM_007399 Q6NZC0
Rat Adam10 NM_019254 NP_062127
ADAM17 Human ADAM17 XM_011510375 P78536
Mouse Adam17 NM_009615 Q9Z0F8
Rat Adam17 NM_020306 NP_064702
View all ADAM Gene Data »

Literature for ADAMs

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
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Cancer Research Product Guide
Immunology Product Listing

A collection of over 190 products for immunology research, the guide includes research tools for the study of:

  • Chemokine and Cytokine Signaling
  • Chemotaxis
  • Complement System
  • Immune Cell Signaling
  • Inflammation
Request copy | Download PDF | View all Product Guides & Listings
Immunology Product Listing
Neurodegeneration Product Guide

A collection of over 275 products for neurodegeneration research, the guide includes research tools for the study of:

  • Alzheimer's disease
  • Parkinson's disease
  • Huntington's disease
Request copy | Download PDF | View all Product Guides & Listings
Neurodegeneration Product Guide
Alzheimer's Life Science Poster

Written by Alan Palmer and updated in 2015, this poster summarizes structural and functional changes observed in the progression of Alzheimer's disease (AD), as well as classic AD drug targets. The hypotheses behind the neurobiology of AD are discussed alongside the different stages in disease progression. Compounds available from Tocris are listed.

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Alzheimer's Life Science Poster

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Cancer Research Product Guide

Cancer Research Product Guide

Our Cancer Research Guide highlights over 750 products for cancer research. Request copy or view PDF today.

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Neurodegeneration Research Product Guide

Neurodegeneration Product Guide

Our Neurodegeneration guide highlights over 275 products for neurodegeneration research. Request copy or view PDF today.

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Immunology Guide

Immunology Product Listing

Our Immunology listing highlights over 190 products for immunology research. Request copy or view PDF today.

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Alzheimer's Disease: Neurobiology and Drug Targets

Written by Alan Palmer

Alzheimer's Life Science Poster

Our Alzheimer's disease poster summarizes the structural and functional changes observed in the progression of this neurodegenerative disease. Request copy or view PDF today.

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